PB1940: REAL-LIFE EXPERIENCE OF THE IMMUNE RECONSTITUTION IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKAEMIA AND SMALL LYMPHOCYTIC LYMPHOMA TREATED WITH IBRUTINIB.
Authors: Belén Olivares Pérez, Francisco José Jiménez Nájar, Clara Aparicio Pérez, Ana Camila González Teomiro, Alfredo Pacheco Reyes, Margarita Fernández de la Mata
Journal: HemaSphere (2023)

Topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical Background: Chronic Lymphocytic Leukaemia (CLL) is an haematological neoplasm in which there is a clonal expansion of mature B-lymphocytes, leading to an increased risk of infections due to dysregulation of the immune system mainly caused by hypogammaglobulinemia. The arrival of targeted therapies has revolutionised the management of this disease. Bruton’s tyrosine kinase inhibitors, such as ibrutinib, have increased progression-free survival and overall survival in these patients. It has also been observed that ibrutinib produces a partial reconstitution of humoral immunity essentially at the expense of an increase in IgA, which has been correlated with a decrease in the risk of infections, especially bacterial infections. Aims: To compare immunoglobulin levels before and during ibrutinib treatment, as well as the number and type of infections and their correlation with immunoglobulin level throughout treatment. Methods: We conducted a retrospective study of the 76 patients diagnosed with CLL and small lymphocytic lymphoma (SLL) in our centre and treated with ibrutinib from November/2015 to February/2022. Patients who had been treated for less than 6 months, those with a monoclonal component and those receiving treatment with intravenous immunoglobulins were excluded, so the analysis was performed on 62 patients. Patient characteristics were analysed and we collected immunoglobulin levels before and during the first two years of treatment as well as infections and their severity over the same period of time. The IBM SPSS Statistics v.20 software was used for the database and statistical analyses. Results: Among a total of 62 patients analysed, 34 (54.8%) had infections and 14 of them (22.5%) required hospitalisation. Patient characteristics are listed in table 1. The median immunoglobulin level before treatment was: IgA 87 mg/dl; IgG 677 mg/dl; IgM 34 mg/dl, with an increase in immunoglobulin levels over the course of ibrutinib treatment, which was statistically significant in the case of IgA (Table 2) (Figure 1).Regarding the association between immunoglobulin levels and the incidence of infections, our analysis showed that there is a statistically significant linear correlation between the increase in IgA level and the decrease in the number of grade III/IV bacterial infections (rho= -0.343, p=0.037), as well as between IgG level and the number of bacterial infections of any grade (rho= -0.393, p=0.038). Overall, there was a decrease in the number of patients with bacterial infections during ibrutinib treatment, 14 in the first 6 months and 6 after 2 years, as well as a decrease in the severity of these infections. Details of the infections are shown in table 3. Summary/Conclusion: Infections in CLL remain a major clinical problem. Treatment with ibrutinib contributes to a partial reconstitution of the humoral immunity of these patients. In our series, we observed an increase in immunoglobulin levels, mainly IgA and IgG, during treatment with ibrutinib and this also leads to a decrease in the number and severity of the infections in our patients.Keywords: Infection, Immune reconstitution, Chronic lymphocytic leukemia, ibrutinib